A Flash Thermal Racemization Protocol for the Chemoenzymatic Dynamic Kinetic Resolution and Stereoinversion of Chiral Amines

A highly practicaland effective 'Flash Thermal Racemization'(FTR) protocol was developed in continuous flow, without needing abase or a H donor. This can be integrated with an enzyme to enablethe chemoenzymatic kinetic resolution of primary amines to be achievedin a more atom-efficient manner without additives. An unprecedentedspace-time yield of up to 1362 & mu;mol mL(-1) h(-1) can be achieved for the dynamic kinetic resolutionof 1-aminoindane, which is at least 10 times more productive thanpreviously reported, and up to 1700-fold more productive when thePd catalyst loading is taken into account. With a slight modification,the flow reactor system can also be used to convert an optically activeamine to its opposite enantiomer.